This research has two basic objectives: 1) The cultivation of pathogenic Treponema pallidum in tissue culture. We plan to investigate whether the Nichols pathogenic strain of T. pallidum as well as other pathogenic strains are capable of surviving and ultimately replicating in our gradient and shell vial tissue culture systems. We will investigate strains of T. pallidum originally isolated from patients with venereal syphilis and endemic nonvenereal syphilis as well as T. pertenue from patients with yaws. We will also attempt to cultivate T. pallidum in tissue culture using microcarrier DEAE-dextran beads. These will be used as a nonenzymatic, nontraumatic method for passaging tissue cell-associated treponemes. 2) Studies on the genetics of T. pallidum. We have shown that treponemal DNAs labeled with 125I can be used in DNA homology assays to study the genetic relationship between T. pallidum (Nichols) and strains of nonpathogenic cultivable treponemes. This line of research will be extended in our investigation of the genetic among strains of the pathogenic treponemes T. pallidum (strains from venereal and nonvenereal syphilis), T. pertenue (yaws), and the rabbit-derived T. paraluis-cuniculi (venereal spirochetosis). We will also study the genetic relationship between T. pallidum and the cultivable nonpathogenic human oral treponemes T. denticola and T. macrodentium as well as the relationships among the cultivable treponemes themselves.